Giacometti A, Quartaroli M, Gaviraghi G, Micheli D, Trist D
Glaxo Research Laboratories, Verona, Italy.
J Pharmacol Exp Ther. 1992 Dec;263(3):1241-7.
The calcium antagonist activity of the long-acting 1,4-dihydropyridine (DHP) lacidipine has been analyzed in rabbit ear artery (REA) and rabbit basilar artery (RBA). Its potency has been estimated from its interaction with BAY K 8644 using a three state gating model of the voltage-operated calcium channel. As a contractile agent, BAY K 8644 exhibited a bell-shaped concentration-response curve in both arteries. For fitting purposes, a second binding interaction between BAY K 8644 and the channel has been used to describe the descending part of the curve. The K(app)s for lacidipine and three other DHPs (nifedipine, nitrendipine and amlodipine) have been compared to pA2 values obtained from displacement of calcium concentration-response curves. In both REA and RBA the K(app)s for the four DHPs were not significantly different compared to their pA2s. The pK(app) values for lacidipine were estimated as 9.80 for REA and 10.20 for RBA.
长效1,4 - 二氢吡啶（DHP）拉西地平的钙拮抗剂活性已在兔耳动脉（REA）和兔基底动脉（RBA）中进行了分析。利用电压门控钙通道的三态门控模型，通过其与BAY K 8644的相互作用对其效价进行了估计。作为一种收缩剂，BAY K 8644在两条动脉中均呈现出钟形浓度 - 反应曲线。为便于拟合，BAY K 8644与通道之间的第二种结合相互作用被用于描述曲线的下降部分。已将拉西地平及其他三种二氢吡啶类药物（硝苯地平、尼群地平和氨氯地平）的表观解离常数（K(app)）与从钙浓度 - 反应曲线位移获得的pA2值进行了比较。在REA和RBA中，四种二氢吡啶类药物的K(app)与其pA2值相比均无显著差异。拉西地平在REA中的pK(app)值估计为9.80，在RBA中为10.20。
